【摘要】 目的 探讨黏蛋白MUC1、MUC4和MUC6组合表达对胰腺癌预后的分层意义及潜在的分子机制。方法 171例患者MUC1、MUC4和MUC6的mRNA数据下载自癌症基因组图谱数据库（TCGA），临床队列数据收集自2006年至2016年在福建医科大学第一附属医院连续性并接受手术切除的168例患者，用免疫组织化学方法检测MUC1、MUC4和MUC6的表达，统计学分析黏蛋白组合表达与总生存期（overall survival, OS）的关系，并筛选显著差异表达基因进行基因本体富集分析。结果 胰腺癌组织中MUC1、MUC4和MUC6的mRNA和蛋白表达水平均高于正常胰腺组织，MUC1异常表达与较高的组织学分级、pN分期呈正相关，而MUC6高表达与组织学分级和淋巴血管浸润呈负相关。Kaplan-Meier分析显示MUC1异常表达和MUC4高表达提示胰腺癌患者预后不良，多因素分析显示MUC4高表达是胰腺癌患者OS的独立预后不良因素。MUC1蛋白与MUC4或MUC6组合表达能分层胰腺癌预后作用，值得注意的是，无论mRNA还是蛋白表达水平，联合3种黏蛋白表达组合均对胰腺癌预后有分层意义。显著相关差异表达基因本体富集分析显示MUC1、MUC4和MUC6生物学功能与质膜信号受体、离子通道和免疫反应等途径有关。结论 MUC1、MUC4和MUC6组合表达有望成为胰腺癌患者的预后指标。更多还原

【Abstract】 Objective This study was to explore the role of combined MUC1, MUC4 and MUC6 expression on pancreatic adenocarcinoma(PAAD) prognosis stratification and its potential molecular mechanism. Methods mRNA levels of MUC1, MUC4 and MUC6 in 171 cases were downloaded from The Cancer Genome Atlas and protein expression detection with immunohistochemical was performed in samples from 168 cases of clinical cohort. Associations between the MUC1, MUC4 and MUC6 with the clinical pathological features and overall survival(OS) were analyzed. Also, significantly differentially expressed genes(DEGs) were picked out for gene ontology(GO) enrichment analysis. Results MUC1, MUC4 and MUC6 exhibited higher level of both mRNA and protein expression in tumor tissues compared to normal pancreatic tissues. Aberrant expression of MUC1 protein was significantly positive association with higher histological grade, increasing pN stage, whereas MUC6 high expression was associated with lower histological grade and absence of lymphovascular invasion. Kaplan-Meier analysis showed aberrant MUC1 status and MUC4 high expression, indicating poor outcomes in PAAD patients. In multivariate analysis, MUC4 high expression was an independent adverse factor of OS for PAAD. Expression of MUC1 protein combination with MUC4 or MUC6 status both exhibited prognostic value. Notably, combinatorial profiling of these three mucins expression had dramatically power for prognostic stratification in PAAD either for mRNA or protein expression. Among the notable GO enriched function analysis for DEGs, biological activities including regulation of plasma membrane receptors, ion channels and immune response were the more significant ones. Conclusion Combined expression of MUC1, MUC4 and MUC6 serves as a promising prognostic marker for PAAD that will contribute to effective clinical applications.更多还原